An integrated approach to characterize genetic interaction networks in yeast metabolism.
Nat Genet
; 43(7): 656-62, 2011 May 29.
Article
em En
| MEDLINE
| ID: mdl-21623372
ABSTRACT
Although experimental and theoretical efforts have been applied to globally map genetic interactions, we still do not understand how gene-gene interactions arise from the operation of biomolecular networks. To bridge the gap between empirical and computational studies, we i, quantitatively measured genetic interactions between â¼185,000 metabolic gene pairs in Saccharomyces cerevisiae, ii, superposed the data on a detailed systems biology model of metabolism and iii, introduced a machine-learning method to reconcile empirical interaction data with model predictions. We systematically investigated the relative impacts of functional modularity and metabolic flux coupling on the distribution of negative and positive genetic interactions. We also provide a mechanistic explanation for the link between the degree of genetic interaction, pleiotropy and gene dispensability. Last, we show the feasibility of automated metabolic model refinement by correcting misannotations in NAD biosynthesis and confirming them by in vivo experiments.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Regulação Fúngica da Expressão Gênica
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Proteínas de Saccharomyces cerevisiae
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Mapeamento de Interação de Proteínas
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Redes Reguladoras de Genes
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Modelos Genéticos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Hungria